Mammalian SWI/SNF complexes are ATPase-powered nucleosome remodeling assemblies crucial for proper development and tissue specific gene expression. The ATPase activity of the complexes is critical for tumor suppression in mice and humans. The complexes also contain seven or more noncatalytic subunits, only one of which, hSNF5, has been individually identifies as a tumor suppressor thus far. The noncatalytic subunits include p270, which is of particular interest because results from a cDNA tissue array analysis indicate p270 may be deficient in as many as 10% of breast cancers and 30% of kidney cancers. The complexes can also include the alternate ARID1B subunit, which is very closely related to p270, but the product of an independent gene. The respective importance of these proteins in the control of cell proliferation was explored here using an siRNA approach and a cell system that permits analysis of differentiation-associated cell cycle arrest. p270-depleted cells fail to undergo normal cell cycle arrest, and show other characteristics of cells that have failed to undergo arrest, such as upregulation of cyclins, increased cdk activity, and failure to induce cdk inhibitors. In contrast, cells depleted ARID1B-containing complexes.

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